Effects of organic and inorganic Ca antagonists on rat platelet arachidonic acid metabolism in the presence of Ca2+, Sr2+ and Ba2+.

The effects of Ca-antagonists on the thrombin-induced mobilization of radiolabeled arachidonate preincorporated into rat platelets as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products were analyzed in the presence of either Ca2+ or Ca2+-substitutes, Sr2+ and Ba2+. Results indicate that following thrombin stimulation (0.2 U/ml) in the presence of Ca2+, nitrendipine (Nit), Cd2+ or Mn2+ reduced the release of arachidonate and the biosynthesis of thromboxane B2. Inhibition of arachidonic acid release and metabolism were also obtained by both Nit and Cd2+ in the presence of Sr2+ and Ba2+. Results from studies with a semi-purified phospholipase A2 fraction prepared from rat platelets indicated that the activity was almost unaffected by Nit or Cd2+. From these findings, we concluded that inhibition of platelet-induced release and metabolism of arachidonic acid by the Ca-antagonists tested require intact platelets. These data support the hypothesis of an interaction of these agents at an unknown surface membrane level.